The standard of care treatment for glioblastoma is surgical resection followed by radiotherapy to 60 Gy with concurrent and adjuvant temozolomide with or without tumor-treating fields. Advanced imaging techniques are under evaluation to better guide radiotherapy target volume delineation and allow for dose escalation. Particle therapy, in the form of protons, carbon ions, and boron neutron capture therapy, are being assessed as strategies to improve the radiotherapeutic ratio. Stereotactic, hypofractionated, pulsed-reduced dose-rate, and particle radiotherapy are re-irradiation techniques each uniquely suited for different clinical scenarios. Novel radiotherapy approaches, such as FLASH, represent promising advancements in radiotherapy for glioblastoma.Glioblastoma remains incurable despite advances in surgery, radiation, and chemotherapy, underscoring the need for new therapies. The genetic heterogenicity, presence of redundant molecular pathways, and the blood-brain barrier have limited the applicability of molecularly targeted agents. The therapeutic benefit seen with a small subset of patients suggests, however, that patient selection is critical. Recent investigations show that molecularly targeted synthetic lethality is a promising complementary approach. The article provides an overview of the challenges of molecularly targeted therapy in adults with glioblastoma, including current trials and future therapeutic directions.Next-generation sequencing of pediatric gliomas has revealed the importance of molecular genetic characterization in understanding the biology underlying these tumors and a breadth of potential therapeutic targets. Promising targeted therapies include mTOR inhibitors for subependymal giant cell astrocytomas in tuberous sclerosis, BRAF and MEK inhibitors mainly for low-grade gliomas, and MEK inhibitors for NF1-deficient BRAFKIAA fusion tumors. Challenges in developing targeted molecular therapies include significant intratumoral and intertumoral heterogeneity, highly varied mechanisms of treatment resistance and immune escape, adequacy of tumor penetrance, and sensitivity of brain to treatment-related toxicities.Mismatch repair (MMR) is a highly conserved DNA repair pathway that is critical for the maintenance of genomic integrity. This pathway targets base substitution and insertion-deletion mismatches, which primarily arise from replication errors that escape DNA polymerase proof-reading function. Here, the authors review key concepts in the molecular mechanisms of MMR in response to alkylation damage, approaches to detect MMR status in the clinic, and the clinical relevance of this pathway in glioblastoma multiforme treatment response and resistance.Glioblastomas (GBMs) exhibit altered metabolism to support a variety of bioenergetic and biosynthetic demands for tumor growth, invasion, and drug resistance. Changes in glycolytic flux, oxidative phosphorylation, the pentose phosphate pathway, fatty acid biosynthesis and oxidation, and nucleic acid biosynthesis are observed in GBMs to help drive tumorigenesis. Both the genetic landscape of GBMs and the unique brain tumor microenvironment shape metabolism; therefore, an understanding of how both intrinsic and extrinsic factors modulate metabolism is becoming increasingly important for finding effect targets and therapeutics for GBM.The definition of glioblastomas has continually evolved from a reliance on strict morphologic features to a combination of histologic and molecular criteria, as the understanding of the genetic basis of these tumors expands. Modern pathologic workup of glioblastomas includes intraoperative evaluations with tissue-sparing techniques, histologic assessment with immunohistochemical markers, and comprehensive molecular characterization aiming at personalized targeting of genetic abnormalities. Machine learning analysis of DNA methylation profiles is a breakthrough technology that has bolstered central nervous system tumor classification and discovery and is particularly beneficial for the diagnosis and subtyping of glioblastomas.This article provides an overview of nonpharmacologic options for the treatment of pain in patients with inflammatory arthritis, such as peripheral spondyloarthritis, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis. The experience of pain in chronic disease is a complex process influenced by multiple domains of health. The discussion focuses on the establishment of a framework for pain control that engages with factors that influence the experience of pain and explores the evidence base that supports specific modalities of nonpharmacologic pain control, such as mindfulness, cognitive behavioral therapy, exercise, massage, splinting, and heat therapy. Rheumatoid and spondyloarthritides are considered separately.The medicolegal landscape of cannabis continues to change, and with ever increasing access there has been a concurrent proliferation of research seeking to understand the utility of cannabinoids in treating innumerable conditions with pain at the forefront. This article seeks to summarize clinically relevant findings in cannabinoid research to better prepare clinicians in the utility of cannabis in the treatment of pain.Rheumatoid arthritis is one of most frequent rheumatic diseases, affecting around 1% of the population worldwide. Pain impacting the quality of life for the patient with rheumatoid arthritis, is often the primary factor leading them to seek medical care. Although sex-related differences in humans and animal models of rheumatoid arthritis are described, the correlation between pain and sex in rheumatoid arthritis has only recently been directly examined. Here we review the literature and explore the mechanisms underlying the expression of the pain phenotype in females and males in preclinical models of rheumatoid arthritis.Pain is a near-universal feature of rheumatoid arthritis, but peripheral joint inflammation may not suffice to explain the etiology of pain in all patients with rheumatoid arthritis. Inflammation in rheumatoid arthritis releases several algogens that may generate pain. Also, central nervous system processes may play a crucial role in the regulation and perpetuation of pain. https://www.selleckchem.com/products/Nafamostat-mesylate.html Several methods for assessing pain in rheumatoid arthritis exist, and recently the role of assessing therapeutics in treating specific etiologies of pain has gained interest.